The first step toward our goal is to improve our understanding of the disease mechanisms involved in AMD, particularly in the early stages. Specifically, we want to study the role of the different components of the immune system in AMD.
To accomplish this we are working on developing a pathophysiologically-relevant animal model of the disease. Our approach exploits the recently discovered genetic association of AMD with a mutation in complement factor H (CFH or Cfh).
- Complement factor H (Cfh) is a key regulator of the complement cascade.
- A point mutation (Y402H) increases the risk of AMD up to 7-fold.
- The “at risk” 402H variant of CFH appears to make AMD patients resistant to anti-VEGF agents and t0 anti-oxidant supplements.
- Despite the obvious anatomical differences, mice CAN develop drusen and CNV.
- We need relevant models of AMD that develop drusen and CNV with high enough frequency to allow for research into the early steps in the pathogenesis.